# Actions of ACE2 along with Nephron to Regulate Blood Pressure

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $540,092

## Abstract

Project Summary
Hypertension affects more than 60 million people in the US and despite its diverse causes,
blockade of the renin-angiotensin system (RAS) lowers blood pressure in the majority of
hypertensive patients. ACE2 is the newest member of the RAS, and our previous work has
established that ACE2 protects against hypertension with actions in the kidney to metabolize
angiotensin II, thus regulating the RAS. As part of our overall goal of understanding how the
RAS impacts BP, we have employed cell-specific gene-targeting and kidney cross-
transplantation in mice to identify the key cellular sources of ACE2 for BP regulation. We found
that mice lacking ACE2 specifically from the proximal tubule (PTACE2KO), the cell type with
highest expression of ACE2 in the kidney, have exaggerated BP elevation in the early phase of
angiotensin II hypertension, associated with enhanced accumulation of angiotensin II peptide in
kidney and ≈50% reduction in urinary excretion of sACE2. Based on kidney cross-
transplantation experiments, the development of hypertension was associated with significant
reductions in sACE2 in both serum and urine whereas sACE2 appeared to normalize BP in
mice lacking renal expression. Thus, our findings suggest ACE2 originating from the PT of the
kidney plays a key role in the initiation of angiotensin II-dependent hypertension, and that kidney
and systemic tissues both contribute to sACE2 in urine. Our new data expand knowledge of
how ACE2 can impact the RAS and BP. This revised proposal aims to define molecular
mechanisms contributing to hypertension in PTACE2KO mice; establish relative contribution of
extra-renal ACE2 and shedding to BP regulation and vascular function with new animal models;
and delineate mechanism by which ACE2 reaches the lumen of the nephron to balance the
RAS. We anticipate our studies will shift the existing paradigm around how ACE2 functions to
regulate BP and moderate kidney function with high relevance to disease states where ACE2 is
dysregulated.

## Key facts

- **NIH application ID:** 10880676
- **Project number:** 5R01DK098382-10
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Susan Bailey Gurley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $540,092
- **Award type:** 5
- **Project period:** 2023-10-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880676

## Citation

> US National Institutes of Health, RePORTER application 10880676, Actions of ACE2 along with Nephron to Regulate Blood Pressure (5R01DK098382-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10880676. Licensed CC0.

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